It may seem useless to propose preventive measures for a disease without established pathogenesis and successful therapy, such as amyotrophic lateral sclerosis (ALS). However, we will show that ALS shares essential molecular mechanisms with aging and that established anti-aging strategies, such as healthy diet or individually adjusted exercise, may be successfully applied to ameliorate the condition of ALS patients. These strategies might be applied for prevention if persons at ALS risk could be identified early enough. Recent research advances indicate that this may happen soon.

Amyotrophic lateral sclerosis (ALS) is a fast progressing neurodegenerative disease leading to quadriplegia, anarthria and respiratory insufficiency. A large variety of phenotypes and disability progression requires individually tailored management. Identification of predictors of poor prognosis may not only improve management, but also allow for more precise patients' stratification for clinical trials or research studies. The aim of the study was to investigate the influence of emotional lability present at disease onset on ALS progression by exploring its direct impact on the decay of the ALS Functional Rating Scale-Revised (ALSFRS-R). The study was performed in a group of 1145 patients from Germany, Poland, Portugal and Turkey between 2014 and 2018. The analysis showed that the presence of emotional lability at ALS onset was linked to a faster decline of ALSFRS-R (0.70 vs 0.50, p<0.0001), in case of either bulbar (0.80 vs 0.65, p<0.05) or limb disease onset (0.59 vs 0.46, p <0.01). It was most prominent in the bulbar subscore of ALSFRS-R. A multiple regression analysis showed a direct influence of emotional lability at ALS onset on disease progression, regardless of age, gender, site of onset, weight loss, cognitive impairment and diagnosis delay (β=0.071; p=0.019). It can therefore be concluded that the presence of emotional lability at the disease onset is an independent factor of faster disease progression in ALS.

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The rationale for this article is a description of a unique, familial case of a patient with amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disorder of unknown etiology coexisting with Klippel–Feil syndrome (KFS), a congenital malformation of cervical vertebrae, characterized by a fusion of minimum 2 cervical vertebrae.We report a 68-year-old man with moderate dysarthria, fasciculations, short neck, hearing deficit, and low posterior hairline. Definite ALS was diagnosed based on neurological abnormalities and electromyography results. Magnetic resonance imaging and computed tomography showed bony abnormalities of the craniocervical junction, fusion of 2 cervical vertebrae, and syringomyelia at the level of C6-C7. KFS phenotype was noted in 2 more family members, and patient's stepsister with KFS phenotype died due to ALS.The pedigree of our family suggests an autosomal-dominant inheritance of both syndromes. Cosegregation of ALS and KFS with an autosomal-dominant trait suggests an impairment of transforming growth factor β signaling pathway, and its potential role is discussed. Further evaluation of patients with autosomal-dominant and sporadic KFS by genetic testing, biochemical measurements, such as plasma transforming growth factor β1, and systematic follow-up electromyography seems warranted.